The main thrust of the proposed work is the design and development of new synthetic methods and reagents and their application to the synthesis of cytotoxic sesquiterpenes, sesquiterpene synthons, and related cancer chemotherapeutic agents. Proposed work includes: a) studies on new methods for the synthesis of pseudoguaianes; b) studies on a chiral germacrane synthesis based on the olefin metathesis strategy; c) studies on fused-ring synthesis based on the olefin metathesis-transannular ene sequence; d) studies on the development of alpha-ketocarbonium on equivalents and the application of the chemistry to projects a) and d); and e) studies on the total synthesis of ingenane, daphnane, and tigliane natural products.